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1.
Eur Urol Focus ; 6(1): 17-25, 2020 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-31255618

RESUMO

CONTEXT: Bone metastasis is a common site of metastatic disease in patients with genitourinary malignancies. Given that the presence of bone metastasis decreases survival and has a negative impact on quality of life impact, it is critical to optimize management of this patient population. OBJECTIVE: To systematically review literature on the systemic treatment of bone metastasis in prostate cancer, renal cell carcinoma, urothelial carcinoma, and germ cell tumors. EVIDENCE ACQUISITION: We performed a nonsystematic critical review of PubMed/Medline, clinicaltrials.gov, and the Cochrane Library from January 2001 to February 2019. Identified reports were reviewed according to the Consolidated Standards of Reporting Trials, and selected based on reporting skeletal related events and symptomatic skeletal events for patients with urologic malignancies. EVIDENCE SYNTHESIS: Skeletal metastases occur frequently in genitourinary malignancies, at rates around 80% for patients with metastatic prostate cancer and 30% for patients with metastatic renal cell and urothelial carcinoma, and are uncommon in patients with germ cell tumors. Skeletal related events and symptomatic skeletal events can occur in these patients. Optimization of bone health involves dietary and lifestyle modifications, and use of osteoclast-targeted agents in select individuals. Additionally, disease-modifying agents, such as radiopharmaceutical, immunotherapy, and cMET inhibitors, which have activity in the bone, have improved outcomes for patients, including skeletal-related events and symptomatic skeletal events. CONCLUSIONS: While the presence of bone metastases is associated with increased mortality and worse outcomes in patients with genitourinary malignancies, strategies have been developed to improve quality of life and survival for patients with skeletal metastases. Future studies investigating novel therapeutic options and bone supporting agents are warranted to target this patient population. PATIENT SUMMARY: In this report, we reviewed the current literature and recent clinical trials involving treatment of bone metastases in urinary cancers. The use of bone-targeting agents can improve outcomes for patients, and additional lifestyle modification can optimize bone health in this population.


Assuntos
Neoplasias Ósseas/secundário , Neoplasias Ósseas/terapia , Carcinoma de Células Renais/secundário , Neoplasias Renais/patologia , Neoplasias da Próstata/patologia , Humanos , Masculino
2.
Cancer Chemother Pharmacol ; 73(6): 1241-52, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24718982

RESUMO

PURPOSE: This study assessed the cardiovascular safety of cabazitaxel, based on thorough evaluation of QT and non-QT variables, and the relationship between pharmacokinetic and pharmacodynamic electrocardiographic (ECG) profiles and the occurrence of Grade ≥3 cardiovascular adverse events. METHODS: Patients with advanced solid tumors were treated with cabazitaxel 25 mg/m(2) every 3 weeks. Digital ECG recordings were obtained during Cycle 1 over 24 h after dosing. The primary end point was effect of cabazitaxel on QT interval corrected by the Fridericia formula (QTcF). Secondary end points were additional ECG parameters (QT, PR and QRS intervals, and heart rate), plasma pharmacokinetics of cabazitaxel and overall clinical safety. RESULTS: The pharmacodynamic (ECG) population included 94 patients. In 63 patients with a full 24-h ECG evaluation, the maximum upper bound of 90 % confidence interval (CI) for mean QTcF change from baseline was 7.46 ms (mean 4.8 ms), occurring at 1 h 30 min post-infusion. The slope of QTcF change from baseline versus cabazitaxel concentration was slightly negative (-0.012 [95 % CI -0.017; -0.008], equivalent to a 1.2 ms decrease per 100 ng/mL increase in cabazitaxel concentration). For non-QT variables, no effect was noted. No Grade ≥3 cardiac adverse events were observed; Grade ≥3 hypotension and lymphocele occurred in two patients and one patient, respectively. CONCLUSION: These results suggest that cabazitaxel has no clinically significant cardiovascular adverse effects in patients with advanced solid tumors.


Assuntos
Eletrocardiografia/efeitos dos fármacos , Coração/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Taxoides/efeitos adversos , Taxoides/uso terapêutico , Adulto , Idoso , Relação Dose-Resposta a Droga , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/patologia , Estudos Prospectivos
3.
Int J Radiat Oncol Biol Phys ; 78(2): 435-41, 2010 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-19939580

RESUMO

PURPOSE: To report on the acute and late gastrointestinal (GI) and genitourinary (GU) toxicity associated with a unique technique of image-guided radiotherapy (IGRT) in patients undergoing postprostatectomy irradiation. METHODS AND MATERIALS: Fifty patients were treated with intensity-modulated radiation therapy (IMRT) after radical prostatectomy. Daily image guidance was performed to localize the prostate bed using kilovoltage imaging or cone-beam computed tomography. The median prescription dose was 68 Gy (range, 62-68 Gy). Toxicity was graded every 3 to 6 months according to the Common Terminology Criteria for Adverse Events version 3.0. RESULTS: The median follow-up was 24 months (range, 13-38 months). Grade 2 acute GI and GU events occurred in 4 patients (8%) and 7 patients (14%), respectively. No Grade 3 or higher acute GI or GU toxicities were observed. Late Grade 2 GI and GU events occurred in 1 patient (2%) and 8 patients (16%), respectively. Only a single (2%) Grade 3 or higher late toxicity was observed. CONCLUSIONS: Image-guided IMRT in the postprostatectomy setting is associated with a low frequency of acute and late GI/GU toxicity. These results compare more favorably to radiotherapy techniques that do not use in-room image-guidance, suggesting that daily prostate bed localization may reduce the incidence of adverse events in patients undergoing postprostatectomy irradiation.


Assuntos
Trato Gastrointestinal/efeitos da radiação , Neoplasias da Próstata/radioterapia , Lesões por Radiação/patologia , Radioterapia de Intensidade Modulada/efeitos adversos , Sistema Urogenital/efeitos da radiação , Idoso , Tomografia Computadorizada de Feixe Cônico , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Período Pós-Operatório , Prostatectomia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Dosagem Radioterapêutica , Radioterapia Adjuvante/métodos , Radioterapia de Intensidade Modulada/métodos , Terapia de Salvação/métodos , Índice de Gravidade de Doença
4.
J Clin Oncol ; 27(11): 1800-5, 2009 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-19255312

RESUMO

PURPOSE: We sought to characterize the pharmacokinetics (PK) and determine a tolerable dose of oral sorafenib in patients with hepatic or renal dysfunction. PATIENTS AND METHODS: Patients were assigned to one of nine cohorts: cohort 1, bilirubin < or = upper limit of normal (ULN) and AST < or = ULN and creatinine clearance (CC) > or = 60 mL/min; cohort 2, bilirubin more than ULN but < or = 1.5x ULN and/or AST more than ULN; cohort 3, CC between 40 and 59 mL/min; cohort 4, bilirubin more than 1.5x ULN to < or = 3x ULN (any AST); cohort 5, CC between 20 and 39 mL/min; cohort 6, bilirubin more than 3x ULN to 10x ULN (any AST); cohort 7, CC less than 20 mL/min; cohort 8, albumin less than 2.5 mg/dL (any bilirubin/AST); and cohort 9, hemodialysis. Sorafenib was administered as a 400-mg dose on day 1 for PK, and continuous daily dosing started on day 8. RESULTS: Of 150 registered patients, 138 patients were treated. With the exception of cohorts 6 and 7, at least 12 patients per cohort were assessable, and the dose level with prospectively defined dose-limiting toxicity in less than one third of patients by day 29 was considered tolerable. No significant associations between the sorafenib PK and cohort were found. CONCLUSION: We recommend the following empiric sorafenib starting doses by cohort: cohort 1, 400 mg twice a day; cohort 2, 400 mg twice a day; cohort 3, 400 mg twice a day; cohort 4, 200 mg twice a day; cohort 5, 200 mg twice a day; cohort 6, not even 200 mg every third day tolerable; cohort 7, not defined; cohort 8, 200 mg each day; and cohort 9, 200 mg each day.


Assuntos
Antineoplásicos/farmacocinética , Benzenossulfonatos/farmacocinética , Insuficiência Hepática/complicações , Neoplasias/tratamento farmacológico , Piridinas/farmacocinética , Insuficiência Renal/complicações , Administração Oral , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Benzenossulfonatos/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/complicações , Niacinamida/análogos & derivados , Compostos de Fenilureia , Piridinas/administração & dosagem , Sorafenibe , Resultado do Tratamento , Adulto Jovem
5.
Radiother Oncol ; 88(1): 20-5, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18524399

RESUMO

OBJECTIVES: To report our experience using Image-Guided Radiation Therapy (IGRT) in patients undergoing post-prostatectomy irradiation. METHODS: Twenty-six patients were treated with radiotherapy following radical prostatectomy using Intensity Modulated Radiation Therapy (IMRT). Prostate bed localization was done using image guidance to align surgical clips relative to the reference isocenter on the planning digitally reconstructed radiographs. Assuming surgical clips to be surrogate for prostate bed, daily shifts in their position were calculated after aligning with the bony anatomy. Shifts were recorded in three dimensions. The acute toxicity was measured during and after completion of treatment. RESULTS: The average (standard deviation) prostate bed motion in anterior-posterior, superior-inferior and left-right directions were: 2.7mm (2.1), 2.4mm (2.1) and 1.0mm (1.7), respectively. The majority of patients experienced only grade 1 symptoms, two patients had grade 2 symptoms and none had grade 3 or higher acute toxicity. CONCLUSIONS: Daily IGRT is recommended for accurate target localization during radiation delivery to improve efficacy of treatment and enhance therapeutic ratio. Larger studies with longer follow-up are necessary to make definitive recommendations regarding magnitude of margin reduction around clinical target volume.


Assuntos
Prostatectomia , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/cirurgia , Radiografia Intervencionista , Planejamento da Radioterapia Assistida por Computador , Radioterapia Adjuvante/métodos , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Dosagem Radioterapêutica , Radioterapia Adjuvante/efeitos adversos , Terapia de Salvação , Tomografia Computadorizada por Raios X , Resultado do Tratamento
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